Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Not Recruiting

Trial ID: NCT00265941


RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer. PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

Official Title

A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas

Stanford Investigator(s)

Quynh-Thu Le, MD
Quynh-Thu Le, MD

Katharine Dexter McCormick and Stanley McCormick Memorial Professor and Professor, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS)

Harlan Pinto
Harlan Pinto

Associate Professor of Medicine (Oncology) and of Otolaryngology - Head & Neck Surgery


Inclusion criteria:

   - Pathologically (histologically or cytologically) proven (from primary lesion and/or
   lymph nodes) diagnosis of squamous cell carcinoma of the oropharynx, hypopharynx, or

   - Selected stage III or IV disease (T2N2-3M0, T3-4 any N M0); Note: Patients with T1,
   any N, or T2N1 tumors are not eligible.

   - Appropriate stage for protocol entry, including no distant metastases, based upon the
   following minimum diagnostic workup:

   - History/physical examination within 4 weeks prior to registration, including
   assessment of weight and weight loss in past 6 months and an examination by a Medical

   - Chest x-ray (or Chest CT scan or PET/CT scan) within 6 weeks prior to registration;

   - CT scan or MRI of the head and neck (of the primary tumor and neck nodes) or PET/CT
   scan within 6 weeks prior to registration; see Section 6.11 for details of PET scans.
   Note: A PET/CT can only be used instead of a CT scan or MRI if the CT is a high
   quality scan with contrast.

   - Left ejection fraction determined by echocardiogram and/or multiple gated acquisition
   (MUGA) technique within 12 weeks of registration;

   - Zubrod Performance Status 0-1;

   - Age > 18;

   - Adequate bone marrow function, defined as follows:

   - Absolute neutrophil count (ANC) > 1,800 cells/mm3 based upon CBC/differential obtained
   within 2 weeks prior to registration on study;

   - Platelets > 100,000 cells/mm3 based upon complete blood count (CBC)/differential
   obtained within 2 weeks prior to registration on study;

   - Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to
   registration on study (Note: The use of transfusion or other intervention to achieve
   Hgb > 8.0 g/dl is acceptable.)

   - Adequate hepatic function, defined as follows:

   - Bilirubin < 1.5 mg/dl within 2 weeks prior to registration on study; For patients with
   Gilbert's disease as the sole cause of elevated bilirubin, please contact the PI, Dr.

   - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x the upper
   limit of normal within 2 weeks prior to registration on study;

   - Adequate renal function, defined as follows:

   - Serum creatinine < 1.5 mg/dl within 2 weeks prior to registration

   - Creatinine clearance (CCr) ≥ 50 ml/min within 2 weeks prior to registration determined
   by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age)
   x (wt in kg)]/[(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)

   - Pregnancy test within 2 weeks prior to registration for women of childbearing

   - Women of childbearing potential and male participants must agree to use a medically
   effective means of birth control throughout their participation in the treatment phase
   of the study (until at least 60 days following the last study treatment);

   - Patient must sign study specific informed consent prior to study entry.

Exclusion criteria:

   - Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
   for a minimum of 3 years;

   - Patients with simultaneous primaries or bilateral tumors are excluded.

   - Gross total excision (e.g., by tonsillectomy) of the primary tumor; however, partial
   removal of the tumor to alleviate an impending airway obstruction does not make the
   patient ineligible.

   - Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
   different cancer is allowable;

   - Prior radiotherapy to the region of the study cancer that would result in overlap of
   radiation therapy fields;

   - Primary site of tumor of oral cavity, nasopharynx, sinuses, or salivary glands;

   - Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal
   sampling of neck disease; radical or modified neck dissection is not permitted.

   - Severe, active co-morbidity, defined as follows:

   - Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable
   angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive
   heart failure, and cardiomyopathy with decreased ejection fraction;

   - Left Ventricular Ejection Fraction < 45%;

   - Transmural myocardial infarction within the last 6 months;

   - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of

   - Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
   requiring hospitalization or precluding study therapy at the time of registration;

   - Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
   Control and Prevention (CDC) definition; note, however, that HIV testing is not
   required for entry into this protocol. The need to exclude patients with AIDS from
   this protocol is necessary because the treatments involved in this protocol may be
   significantly immunosuppressive. Protocol-specific requirements may also exclude
   immuno-compromised patients.

   - Any uncontrolled condition, which in the opinion of the investigator, would interfere
   in the safe and timely completion of study procedures;

   - CTCAE, v. 3.0 grade 3-4 electrolyte abnormalities:

      - Calcium < 7 mg/dl or > 12.5 mg/dl;

      - Glucose < 40 mg/dl or > 250 mg/dl;

      - Magnesium < 0.9 mg/dl or > 3 mg/dl;

      - Potassium < 3 mmol/L or > 6 mmol/L;

      - Sodium < 130 mmol/L or > 155 mmol/L

   - Pregnant or lactating women or women of childbearing potential and men who are
   sexually active and not willing/able to use medically acceptable forms of
   contraception; this exclusion is necessary because the treatment involved in this
   study may be significantly teratogenic.

   - Prior allergic reaction to the study drug(s) involved in this protocol;

   - Prior therapy that specifically and directly targets the EGFR pathway;

   - Prior severe infusion reaction to a monoclonal antibody.


drug: cisplatin

drug: cetuximab

radiation: Accelerated Fractionation by Concomitant Boost

radiation: Intensity-modulated radiation therapy

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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